Anti-Ischemia Drugs Flashcards
1
Q
What are the main determinants of oxygen supply to heart?
How are they impaired?
How is this fixed?
A
- Blood flow
- O2 carrying capacity of blood
Impaired by…
- Dec coronary perfusion pressure, inc coronary resistance, inc extrinsic compressive forces
- emphysema, pneumonia, change in altitude (less O2 supply)
- anemia or sickle cell (change Hb content)
Fix by…
- Inc oxygen supply, inc hematocrit
- Vasodilate coronary arteries
- Maintain BP to maintain coronary perfusion pressure
2
Q
What are the main determinants of oxygen demand of heart?
How are these increased?
How is this fixed?
A
- Inc HR
- Inc Contractility
- Inc wall stress (greater P or V)
Increased if…
- adrenergics/symp NS
- anything that inc preload (vol) or after load (pressure)
Fix by…
- Dec HR
- Dec Ca++ influx
- Dec preload
- Dec afterload
3
Q
Exogenous Nitrates in General (mechanism, types & dose dependence)
A
- MAO - converted to NO by mitochondrial aldehyde dehydrogenase
- Depends on dose
- @ low dose… venous dilation
- @ high dose … coronary artery dilation
- Short acting - mucosal (sublingual or oral spray) or transdermal (ointment) —> dir to blood so rapid onset that can be used for angina as needed; can also use prophylactically b/f activities that trigger angina
- Long acting - oral or sustained release patch
4
Q
Positive Oxygen Effects of Nitrates
A
Dec coronary resistance, dec R3 b/c less preload, dec preload and after load so less wall tension (less demand)
5
Q
5 Side Effects of Nitrates
A
- Nitrate tolerance (less potent over time); help by dosing so that they are nitrate free for 10-12 hrs a day (“”resensitization”)
- Headache/flushing - usually go away after 2 wks
- Hypotension - esp if on diuretic (DO NOT USE IF ALSO ON PDE INHIB - like Viagra)
- Hypoxemia - dilate vessels in hypoxic part of lung instead of oxygenated part of lung
- Tissue hypoxia if methemoglobinemia (rare)
6
Q
What are the 2 long-acting nitrates? How do they differ?
A
- Isosorbide dinitrate - hepatic 1st pass —> isosorbide mononitrate
- Isosorbide mononitrate - already in active metabolite form so greater bioavailability; FASTER
7
Q
3 Categories of Beta Blockers
A
- Cardioselective
- Intrinsic Sympathomimetics
- Alpha Receptor Blocking
8
Q
Cardioselective Beta Blockers
A
- preferentially block beta 1 (however un-selective @ high doses)
- Atenolol, bisoprolol, betaxolol, esmolol, metoprolol
- Positive effects - dec HR and dec contractility so less demand; dec HR also allows more diastolic filling time so more coronary flow, some inc resistance
9
Q
IAS Beta Blockers
A
- weak beta agonists that competitively inhibit the strong catecholamines from binding (shield from natural catecholamines)
- Pindolol, acebutolol, carteolol, penbutolol
- Do not use if CAD (may inc mortality)
- Pos effects - slight dec in HR and contractility but may inc after load - not used for CAD
10
Q
Alpha Receptor Blocking Beta Blockers
A
- prevent unopposed alpha adrenergic stimulation during beta blockage so no compensatory vasoconstriction
- Labetolol, carvedilol
- Best for HTN
11
Q
5 Side Effects of Beta Blockers
A
- CNS - esp if lipophilic (fatigue, sleep problems, depression, sexual dysfunction)
- Conduction abnormalities - dec SA node rate so brady
- CHF
- Exacerbate peropheral vascular disease
- Dec glycogen breakdown (normally sympathetic beta) so exacerbate DN hypoglycemia
12
Q
Hydrophilic v. Lipophilic Beta Blockers
A
- Lipophilic = liver metabolism so shorter half-life & cross BBB so CNS side effects
- Hydrophilic = renal metabolism so longer half-life & do NOT cross BBB so less CNS effects
13
Q
2 Categories of Ca Channel Blockers
A
- Dihydropyridines - more potent vasodilators
- Non - Dihydro (Benzothiazapines & Phenylalkylamines) - more potent effects on slowing SA and AV node - dec HR and conduction
14
Q
Dihydropyridines
A
- Positive effects - dec coronary vascular resistance and dec R3 thru dilation, dec after load and preload by peripheral dilation so less wall tension
- Can induce reflex tachycardia
- Nifedipine, amlodipine, felodipine, nicardipine, isradipine
15
Q
Non-dihydropyridines
A
- Positive effects - dec coronary resistance still thru vasodilation and dec HR and contractility so less demand
- Can result in symptomatic bradycardia or AV block (esp in verapamil so do not use w/ beta blocker for risk of complete block)
- Diltiazem & verapamil
16
Q
8 Side Effects of Ca Channel Blockers
A
- All hepatic metabolism except Diltiazem (40% renal) so many drug-drug interactions
- Hypotension - esp w/ dihydro
- Exacerbate CHF - esp w/ non-dihydro
- Conduction abnormalities (above)
- Edema - augmented vasodilation
- GI - dec motility b/c smooth muscles relac
- Gingival hyperplasia - rare
- **Cardio mortality risk in short-acting nifedipine b/c potent vasodilation —> rapid compensatory adrenergic tone (in long-acting still use w/ beta blocker just in case)
17
Q
What is the role of Ranolazine?
A
- MAO- inhibits delayed Na channels (late in AP) and Kr channels in myocardial AP; so dec intracellular Na —> more Na/Ca pump —> dec Ca in cell (less Ca overload - more relaxation)
- SO it dec wall tension by preventing Ca overload in ischemic myocytes
- Positive Effects - Dec R3 /dec wall tension (demand)
18
Q
Ranolazine Side Effects
A
- QT prolongation - b/c inhibits K+; can lead to torsade
- CYP3a metabolism so inc drug if given w/ other drugs that inhibit CYP3a (anti-fungals, anti-retrovirals and antibiotics) or if liver problems —> inc chance of QT prolongation
- Can also inc digoxin levels
19
Q
How to Choose Drugs for Chronic Ischemic Heart Disease Pt
A
- First line - beta blockers WITHOUT ISA (intrinsic sympathetic activity)
- If angina persists… add in long-acting nitrate w/ appropriate nitrate-free interval
- Can also prescribe short-acting nitrate for as needed basis (acute episodes or prophylaxis)
- Use non-dihydro in patients w/ contraindications to beta blockers
- If refractory symptoms - try tri-drug therapy such as ranolzaine
